title: Loss of melanogenic properties in tyrosinases induced by glucosylation inhibitors within malignant melanoma cells.
abstract: Glycosylation inhibitors, glucosamine or tunicamycin, have been found to be specific inhibitory modulators for melanogenesis, which is accentuated generally in malignant melanoma cells. Exposure to glucosamine (1 mg/ml) or tunicamycin (0.2 to 0.4 micrograms/ml) induces a marked pigment loss within melanoma cells in vitro with a decrease in their grown curves. This melanogenic inhibition occurs without a substantial decrease in the synthesis of DNA, RNA, and protein in comparison with a specific, marked suppression of carbohydrate synthesis as revealed by suppressed mannose incorporation into these cells. Assay of tyrosinase of glucosamine- or tunicamycin-induced unpigmented melanoma cells has revealed a selective and marked decrease in the melanosome-rich large-granule fraction, but no substantial decrease in the total activity of remaining subcellular fractions. Electrophoresis of tyrosinase in the 30,000 X g supernatant fraction demonstrates an increase in the T1 form of soluble tyrosinase, while a disappearance of or marked decrease in membrane-bound tyrosinase, T3, is seen in the small- and large-granule fractions. Glycoprotein synthesis in the melanogenic subcellular compartments of pigment cells seems to play an integral role in melanogenesis which is principally enhanced in their carcinogenic status.
mesh_terms: D000818:Animals; D004156:Catechol Oxidase / Q000378:metabolism*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D006224:Cricetinae; D004586:Electrophoresis; D004790:Enzyme Induction / Q000187:drug effects; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis; D008358:Mannose / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008647:Mesocricetus; D051379:Mice; D014442:Monophenol Monooxygenase / Q000032:analysis / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D006023:Glycoproteins; D008543:Melanins; D014415:Tunicamycin; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D005944:Glucosamine; D008358:Mannose